The creation of holographic images using fine diffraction patterns illuminated with laser light is well known. White-light “holograms” are also well known. A common example of Benton white-light “holograms” is the creation of images on credit cards and the like to prevent tampering with information carried on the cards, and to enhance their visual aesthetics. Known images include rainbow-like color patterns, pictures, and changes in color or location of pictures or parts of pictures with a change in viewing angle.
While it is also known to emboss a suitable relief on a section of a generally flat sheet of plastic material, such as that forming a credit card, with a heated metal die, the production of high resolution diffraction reliefs on edible products presents special problems. Materials suitable for receiving and retaining diffraction reliefs on edible products must not only be capable of receiving a fine pattern, e.g., 1,000 to 5,000 lines per mm, and be capable of retaining that fine pattern (be stable), but they must also be food safe and palatable. Retention requires resistance to mechanical degradation during routine handling as well as the adverse effects of water, especially air-borne humidity and heat. Ingestibles should also be digestible, which typically means they should be water-soluble. (Pharmaceutical delivery systems are known which rely on stomach acid to dissolve a coating, or which have a substantially indigestible coating with small holes through which a pharmaceutically active substance is released.)
U.S. Pat. No. 4,668,523 to Begleiter discloses the first system for applying a high resolution diffraction gratings to a food product to produce edible holograms.
While such diffraction reliefs produced by dehydration in molds have proven to be able to provide color and other visual effects on candies and other food products, they have not heretofore been used commercially on dosage forms such as pharmaceuticals. Indeed, the commercial production of small, holographic-bearing dosage forms introduces problems, enumerated below, not encountered using the known general methods for creating holographic foods such as lollipops.
Pharmaceutical products are typically sold and used in a variety of forms, each providing a known unit dosage of a pharmaceutically active ingredient. Typical forms include common compressed powder tablets and coated tablets. The term also includes hard shell capsules and soft-gel capsules. For the purposes of this application, these and other unit dosage delivery forms are termed “dosage forms”. These dosage forms typically include a core which, in turn, include a pharmaceutically active ingredient and a pharmaceutically acceptable inert carrier. In many instances, the dosage form also includes an outer layer that encloses the core, protects it, contains it (e.g., a capsule holding a granular, powdery, or viscous core material), and/or provides a vehicle for carrying a material that facilitates use of the dosage form, e.g., a “buffered” coating on an aspirin tablet.
In the pharmaceutical field, it is important to identify and differentiate one product from another reliably. The consumer needs to be sure of what medicine he/she is taking. The manufacturer is interested in establishing brand identity and extending brand loyalty. It is also of interest to be able to deter counterfeits and to covertly differentiate dosage forms, e.g., for use in double blind tests.
Pharmaceuticals and food products have been limited to the use of certain FDA and other internationally approved colors produced chemically by dyes and lakes. Many countries have different regulations governing the use of these chemicals leading to difficulty in creating uniform product identities for pharmaceutical companies across international borders. Further, it would be desirable to have the capability of producing a greater variety of colors beyond the few that have regulatory approval—especially “rainbow-like” effects produced by the juxtaposition of multiple colors of gradually varying wavelength.
Monitoring of storage conditions is important in preserving product integrity.
“Edible Holography: The application of holographic techniques to food processing”, SPIE, Vol. 1461, “Practical Holography V” (1991) at pages 102–109 discusses the use of a punch die to compress a powder into a tablet while simultaneously using a metal die plate to impress a microrelief as the powder becomes a solid core in a tablet press. Rapid die wear and difficulty in releasing the compressed core from the die are just some of the problems that limit this technique.
More generally, a commercially viable system for holographically conveying information on pharmaceuticals must address a variety of requirements beyond those discussed above for food products. A major difference is that pharmaceutical dosage forms are “non-deposited”, that is, they are not poured into a mold as a liquid to be formed, as with hard candy. Also pharmaceutical dosage forms are small as compared to present commercial edible products such as lollipops, and they can have non-planar outer surfaces where it would be desirable to carry a holographic diffraction pattern. In addition, the material in which the microrelief is formed cannot interact adversely with the pharmaceutically active ingredient(s) to reduce its efficacy, and should not otherwise be objectionable when ingested, e.g., allergenic. The image-producing microrelief on a dosage form must also be reliably durable and stable during manufacture, packaging, shipment, and under acceptable storage conditions, that is, conditions that do not adversely affect the efficacy or required product life of the dosage form. The microrelief should have a long shelf life, which requires a high resistance to changes in shape on the micron scale due to applied mechanical stresses, and degradation due to temperature changes or to the absorption of moisture. Such a microrelief is termed “stable”. If applied as a layer on a core, the layer containing the relief should not delaminate or “bubble”. Bubbling is a particular concern when heat is used in applying or processing the layer.
Suitable microreliefs used on pharmaceuticals should be compatible with modern dosage form manufacturing equipment and techniques and be economical in its implementation. A microrelief must also be non-detrimental to the efficacy of the pharmaceutical. Any heat used as part of the manufacturing process for implementing a microrelief should not degrade the efficacy of pharmaceutically active ingredient(s). While holograms transfer and reconstruct best on flat surfaces, coated tablets with flat faces tend to adhere to one another, or “twin”, during the coating process. The production of diffraction microreliefs on coated products should resist twinning in order to maintain acceptable yield ratios. Suitable microreliefs should also be formed using materials that do not require new regulatory approval.
It is also desirable to know if an ingestible product is likely to have retained its efficacy after it has been manufactured and stored. Stated in other words, it would be useful to have a readily visible indicator of the environmental history of any given dosage form. Such an indicator, for example, would usefully indicate whether a dosage form had been exposed to high temperatures, e.g., over 100° F., and high humidities, e.g., over 80% relative humidity (RH), for any extended period of time during storage or prior to sale or use. This problem is commonly addressed by printing an expiration date on a container for the product. However, it would be better if there was some visual indication of efficacy on the product itself.
It is therefore a principal object of this invention to provide an edible product, including a dosage form in any of a wide variety of shapes and configurations, that has a stable microrelief whose stability can be controlled, and that conveys information such as visual holographic images and effects.
Another principal object is to provide specific, approved materials, methods and apparatus for producing such a product that are cost effective and compatible with modern high-speed production equipment and techniques such as tablet coating apparatuses.
Yet another object of this invention is to provide a system for introducing holographic brand identification for a wide range of edible products in a wide range of forms.
Another object is to provide a visual quality control indication on each dosage form in the form of a hologram that visibly changes if the dosage form has been exposed to severe adverse conditions of temperature or humidity.
A further object is to provide a system for controlling and detecting counterfeit dosage forms.
Still another object is to provide dosage forms with covert identifiers suitable for use in double blind studies.
Another object is to provide the foregoing advantages without requiring a new regulatory approval of the dosage form.
Yet another object is to provide color and visual images and effects for food products and for pharmaceuticals, (1) without the use of FDA regulated colors, dyes, inks, or metals, or (2) with colors other than those which are FDA approved, or (3) with the use of FDA approved colorant only as a contrast color to make holographic effects and images more readily visible.